Method for producing substituted-2-nitroguanidine derivatives

ABSTRACT

The invention relates to a method for producing an organic compound of formula (I) and optionally its E/Z-isomers, E/Z-isomer mixtures and/or tautomers, each in free or salt form, R 1  representing hydrogen or C 1 -C 4  alkyl, R 2  representing hydrogen, C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl or a radical —CH 2 B, Het representing an unsubstituted or substituted heterocyclic radical and B representing phenyl, 3-pyridyl or thiazolyl, these being optionally substituted. The invention is characterized in that a compound of formula (IIa) Q—A—Q, wherein A represents a direct bond or an organic radical, or of formula (IIb), wherein U represents an organic radical, Q representing (1) in the compounds (IIa) and (IIb) and R 1 , R 2  and Het having the meaning given above for formula (I), and optionally their E/Z-isomers, E/Z-isomer mixtures and/or tautomers, each in free or salt form are hydrolyzed. The invention also relates to a method for producing compounds of formulae (IIa), (IIb), (IIIa) and (IIIb), and to a method for combating pests with compounds of formulae (IIa) and (IIb).

The present invention relates to a novel type of method of producingsubstituted 2-nitroguanidine derivatives.

It is known that, in order to produce 1,3-disubstituted2-nitroguanidines, a further substituent may be introduced intomonosubstituted 2-nitroguanidines (e.g. by alkylation) (see e.g. EPpatent applications 0.375.907, 0.376.279 and 0.383.091). Owing to thepresence of three reactive hydrogen atoms in the monosubstituted2-nitroguanidines used as the starting material in these reactions, thepreviously proposed substitution reactions of this kind are oftennon-selective and lead to undesired substitution products. The mentionedEP patent applications describe the production of 1,3-disubstituted2-nitroguanidines by reacting monosubstituted nitroisothioureas withprimary amines whilst cleaving mercaptan. However, thesenitroisothiourea compounds, containing alkylthio leaving groups, whichare proposed as starting compounds in the known processes, can only beobtained with difficulty. In addition, in EP-A-0-483.062, a method ofproducing the compounds of formula (I) by hydrolysis ofhexahydro-triazines is described.

It has now been shown that the above-described methods of producingcompounds of formula (I) do not satisfy the requirements demanded of achemical production process, such as availability, toxicity, stabilityin storage and purity of the starting materials and excipients, reactiontime, energy consumption and volumes yielded by the process, quantityand recovery of the accruing by-products and waste products, as well aspurity and yield of the end product. There is therefore a need toprovide improved methods of producing these compounds. It has nowsurprisingly been found that the method according to the invention isable to satisfy these requirements to a large extent.

Accordingly, it is the aim of the present invention to provide animproved method of producing 1-monosubstituted and 1,3-disubstituted2-nitroguanidines from readily obtainable starting compounds, whichallows specific 1,3-disubstitution without obtaining major amounts ofundesired by-products.

The object of the invention is

a) a method of producing a compound of formula

 and, if appropriate, the E/Z isomers, E/Z isomeric mixtures and/ortautomers thereof, each in free form or in salt form, wherein

R₁ is hydrogen or C₁-C₄-alkyl;

R₂ is hydrogen, C₁-C₆-alkyl, C₃-C₆-cycloalkyl or a radical —CH₂B;

Het is an aromatic or non-aromatic, monocyclic or bicyclic heterocyclicradical which is unsubstituted or—depending on the substitutionpossibilities of the ring system—mono- to penta-substituted bysubstituents selected from the group comprising halogen, C₁-C₃-alkyl,C₁-C₃-alkoxy, halogen-C₁-C₃-alkyl, C_(1-C) ₃-halogenalkoxy, cyclopropyl,halogencyclopropyl, C₂-C₃-alkenyl, C₂-C₃-alkynyl, C₂-C₃-halogenalkenyland C₂-C₃-halogenalkynyl, C₁-C₃-alkylthio, C₁-C₃-halogenalkylthio,allyloxy, propargyloxy, allylthio, propargylthio, halogenallyloxy,halogenallylthio, cyano and nitro; and

B is phenyl, 3-pyridyl or thiazolyl, which are optionally substituted byone to three substituents from the group comprising C₁-C₃-alkyl,C₁-C₃-halogenalkyl, cyclopropyl, halogencyclopropyl, C₂-C₃-alkenyl,C₂-C₃-alkynyl, C₁-C₃-alkoxy, C₂-C₃-halogenalkenyl, C₂-C₃-halogenalkynyl,C₁-C₃-halogenalkoxy, C₁-C₃-alkylthio, C₁-C₃-halogenalkylthio, allyloxy,propargyloxy, allylthio, propargylthio, halogenallyloxy,halogenallylthio, halogen, cyano and nitro;

 characterised by hydrolysing a compound of formula

Q—A—Q  (IIa),

wherein A is a direct bond or an organic radical; or of formula

wherein U is an organic radical; and in compounds (IIa) and (IIb) Qsignifies

and R₁, R₂ and Het are as defined above for formula (I), and optionallythe E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each infree form or in salt form.

The compounds of formula (I) may be present as E/Z isomers, e.g. in thefollowing two isomeric forms

Accordingly, any reference to compounds of formula (I) hereinbefore andhereinafter is understood to include also their corresponding E/Zisomers, even if the latter are not specifically mentioned in each case.

The compounds of formula (I) may be present partly in the form oftautomers. Accordingly, any reference to compounds of formula (I)hereinbefore and hereinafter is understood to include also theircorresponding tautomers, even if the latter are not specificallymentioned in each case.

The compounds of formula (I) and, where appropriate, the E/Z isomers andtautomers thereof, may be present as salts. Compounds of formula (I)having at least one basic centre may form e.g. acid addition salts.These are formed for example with strong inorganic acids, such asmineral acids, e.g. sulfuric acid, a phosphoric acid or a hydrohalicacid, or with strong organic carboxylic acids, such asC₁-C₄alkanecarboxylic acids substituted where appropriate for example byhalogen, e.g. acetic acid, such as optionally unsaturated dicarboxylicacids, e.g. oxalic, malonic, maleic, fumaric or phthalic acid, such ashydroxycarboxylic acids, e.g. ascorbic, lactic, malic, tartaric orcitric acid, or benzoic acid, or with organic sulfonic acids, typicallyC₁-C₄alkane or arylsulfonic acids substituted where appropriate forexample by halogen, e.g. methane-, trifluoromethane- orp-toluene-sulfonic acid. Salts of compounds of formula (I) with acids ofthe said kind are preferably obtained when working up the reactionmixtures.

In a broader sense, compounds of formula (I) with at least one acidgroup can form salts with bases. Suitable salts with bases are forexample metal salts, typically alkali or alkaline earth metal salts,e.g. sodium, potassium or magnesium salts, or salts with ammonia or anorganic amine, such as morpholine, piperidine, pyrrolidine, a mono-, di-or tri-lower alkylamine, e.g. ethyl-, diethyl-, triethyl- ordimethylpropylamine, or a mono-, di- or trihydroxy-lower alkylamine,e.g. mono-, di- or triethanolamine. Corresponding internal salts whereappropriate may also be formed. Preferred compounds within the scope ofthis invention are agrochemically advantageous salts. Hereinbefore andhereinafter, the free compounds of formula (I) are understood whereappropriate to include also by analogy the corresponding salts, or thesalts are understood to include also the free compounds of formula (I).The same applies to E/Z isomers and tautomers of compounds of formula(I) and salts thereof. The free form is preferred.

The statements made about the free compounds of formula (I) or the E/Zisomers and tautomers and salts thereof also apply by analogy to thecompounds of formulae (IIa) and (IIb), as well as the compounds offormulae (IIIa) and (IIIb) below.

In the definitions of the above formulae (I), (IIa), (IIb) and of thecompounds of formulae (IIIa) and (IIIb) below, the individual genericterms are to be understood as follows:

The halogen atoms considered as substituents may be both fluorine andchlorine, and bromine and iodine, whereby fluorine, chlorine and bromineare preferred, especially chlorine. Halogen in this context isunderstood to be an independent substituent or part of a substituent,such as in halogenalkyl, halogenalkylthio, halogenalkoxy,halogencycloalkyl, halogenalkenyl, halogenalkynyl, halogenallyloxy orhalogenallylthio. The alkyl, alkylthio, alkenyl, alkynyl and alkoxyradicals considered as substituents may be straight-chained or branched.Examples of such alkyls which may be mentioned are methyl, ethyl,propyl, isopropyl, butyl, isobutyl, sec.-butyl or tert.-butyl. Suitablealkoxy radicals which may be mentioned are, inter alia: methoxy, ethoxy,propoxy, isopropoxy or butoxy and the isomers thereof. Alkylthio is forexample methylthio, ethylthio, isopropylthio, propylthio or the isomericbutylthio. If the alkyl, alkoxy, alkenyl, alkynyl or cycloalkyl groupsconsidered as substituents are substituted by halogen, they may be onlypartially halogenated or also perhalogenated. The above-mentioneddefinitions apply here to halogen, alkyl and alkoxy. Examples of thealkyl elements of these groups are methyl which is mono- totrisubstituted by fluorine, chlorine and/or bromine, such as CHF₂ orCF₃; ethyl which is mono- to pentasubstituted by fluorine, chlorineand/or bromine, such as CH₂CF₃, CF₂CF₃, CF₂CCl₃, CF₂CHCl₂, CF₂CHF₂,CF₂CFCl₂, CF₂CHBr₂, CF₂CHClF, CF₂CHBrF or CClFCHClF; propyl orisopropyl, mono- to heptasubstituted by fluorine, chlorine and/orbromine, such as CH₂CHBrCH₂Br, CF₂CHFCF₃, CH₂CF₂CF₃ or CH(CF₃)₂; butylor one of its isomers, mono- to nonasubstituted by fluorine, chlorineand/or bromine, such as CF(CF₃)CHFCF₃ or CH₂(CF₂)₂CF₃;2-chlorocyclopropyl or 2,2-difluorocyclopropyl; 2,2-difluorovinyl,2,2-dichlorovinyl, 2-chloroalkyl, 2,3-dichlorovinyl or 2,3-dibromovinyl.

If the defined alkyl, alkoxy or cycloalkyl groups are substituted byother substituents, they may be mono- or repeatedly substituted byidentical or different substituents from those listed. In thesubstituted groups, it is preferable for one or two further substituentsto be present. The cycloalkyl radicals considered as substituents maybe, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.Alkenyl and alkynyl groups contain an unsaturated carbon-carbon bond.Typical representatives are allyl, methallyl or propargyl, but alsovinyl and ethynyl. The double or triple bonds in allyloxy, propargyloxy,allylthio or propargylthio are separated from the connection point tothe hetero atom (O or S) preferably by a saturated carbon atom.

As with the above-mentioned alkyl, alkenyl and alkynyl groups, thealkylene, alkenylene and alkynylene groups defined in the following mayalso be straight-chained or branched. Examples are —CH₂—CH₂—,—CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂—, —CH₂—C(CH₃)H— and —C(CH₃)H—C(CH₃)H—.The alkylene, alkenylene, alkynylene, cycloalkylene, arylene orheterocyclyl groups listed below are, where appropriate, substituted inthe same way as the above-mentioned alkyl, alkenyl and alkynyl groups.

Aryl or arylene signifies phenyl or naphthyl, or phenylene ornaphthylene, especially phenyl or phenylene.

In the context of the present invention, the heteroaryl radicalindicated as Het signifies preferably a 5- to 7-membered, aromatic ornon-aromatic ring with one to three hetero atoms selected from the groupcomprising N, O and S. Preference is given to aromatic 5- and 6-rings,which have a nitrogen atom as the hetero atom and optionally one furtherhetero atom, preferably nitrogen, oxygen or sulphur, especiallynitrogen.

It has now surprisingly been found that the method according to theinvention is able to satisfy the requirements mentioned initially.

The hydrolysis process according to the invention may be carried outboth in an acidic and in a basic medium. In the acidic range, pH valuesof 6 or less, especially 1 to 3, are preferred. In the basic range, a pHvalue greater than 7 and up to 12, especially 8 to 12, in particular 8to 10, is preferred. The reaction is carried out at normal pressure andat a temperature of 0 to 120° C., preferably 20 to 80° C.

The reaction is carried out in a solvent or diluent that is inerttowards the reaction components. Suitable solvents are, in particular,alcohols such as methanol, ethanol, propanol and isopropanol, as well asespecially water. Further appropriate solvents are e.g. ethers, such astetrahydrofuran and dioxane, as well as other solvents which do notadversely affect the reaction. The solvents may also be used asmixtures. A compound of formula (II) is preferably hydrolysed in anaqueous medium or in a mixture of water with an alcohol.

Suitable acids for carrying out the process are preferably mineralacids, e.g. sulfuric acid, a phosphoric acid or a hydrohalic acid, anorganic carboxylic acid, typically C₁-C₄alkanecarboxylic acidssubstituted where appropriate for example by halogen, e.g. acetic acid,such as dicarboxylic acids that are unsaturated where necessary, e.g.oxalic, malonic, maleic, fumaric or phthalic acid, typicallyhydroxycarboxylic acids, e.g. ascorbic, lactic, malic, tartaric orcitric acid, or benzoic acid, or an organic sulfonic acid, typicallyC₁-C₄alkane- or arylsulfonic acids substituted where appropriate forexample by halogen, e.g. methanesulfonic or p-toluenesulfonic acid.

Suitable bases for carrying out the process are preferably hydroxides ofalkali metals and alkaline earth metals, such as NaOH and KOH,carbonates such as Na₂CO₃, NaHCO₃, K₂CO₃; phosphates such as Na₃PO₄,Na₂HPO₄, alcoholates such as sodium methaholate, sodium ethanolate andK-tert.-butanolate, organic amines such as morpholine, piperidine,pyrrolidine, a mono-, di- or tri-lower alkylamine, e.g. ethyl-, diethyl,triethyl- or dimethylpropyl-amine, or a mono-, di- or trihydroxy loweralkylamine, e.g. mono-, di- or triethanolamine, or dialkylaniline, forexample N,N-dimethyl- or N,N-diethylaniline, as well as salts of organicacids, such as sodium acetate, potassium acetate or sodium benzoate, ormixtures thereof, for example acetate or phosphate buffers.

Especially advantageous reaction conditions are described in theexamples.

The method according to the invention is preferably used to producecompounds of formula (I) in which the heterocyclic radical Het isunsaturated and is bonded by a carbon atom as a ring member to thefundamental substance. Especially preferred radicals Het are pyridyl,thiazolyl, tetrahydrofuranyl, dihydrofuranyl, furanyl,N-oxido-pyridinio, oxazolyl, isoxazolyl, thienyl, morpholinyl,piperidinyl, pyridinyl and pyrazinyl; particularly pyridyl, thiazolyl,tetrahydrofuranyl and N-oxido-pyridinio, most particularly 3-pyridyl,2-halogenpyrid-5-yl, 2,3-dihalogenpyrid-5-yl, 2-halogenthiazol-5-yl,tetrahydrofuran-3-yl, 2-methyl-tetrahydrofuran-4-yl, 1-oxopyrid-3-yl,1-oxo-2-halogenpyrid-5-yl and 1-oxo-2,3-dihalogenpyrid-5-yl.

Equally preferably, the heterocycles Het carry one to three substituentsfrom the group halogen, C₁-C₃-alkyl, C₁-C₃-halogenalkyl andC₁-C₃-halogenalkoxy each with 1 to 7 halogen atoms, and C₁-C₃-alkoxy,most preferably chlorine or methyl.

Furthermore, compounds of formula (I) are preferably produced accordingto the invention, in which the radical B is a phenyl, pyridyl orthiazolyl radical that is unsubstituted or may be substituted by one totwo radicals from the group halogen, C₁-C₃-alkyl, C₁-C₃-halogenalkyl andC₁-C₃-halogenalkoxy each with 1 to 7 halogen atoms, and C₁-C₃-alkoxy.

Of the compounds of formula (I) to be produced according to theinvention, the notable ones are those in which

R₁ is hydrogen;

R₂ is hydrogen, C₁-C₃-alkyl or cyclopropyl; especially hydrogen, methyl,ethyl or cyclopropyl, in particular methyl; and

Het is pyridyl, 1-oxopyridyl, tetrahydrofuranyl, thiazolyl; or pyridyl,1-oxidopyridinio, tetrahydrofuranyl or thiazolyl, respectivelysubstituted by one to three substituents from the group halogen,C₁-C₃-alkyl, C₁-C₃-halogenalkyl as well as C₁-C₃-halogenalkoxy with 1 to7 halogen atoms and C₁-C₃-alkoxy;

 especially 2-chloropyrid-5-yl, tetrahydrofuran-3-yl,2-methyl-tetrahydrofuran4-yl or 2-chloro-thiazol-5-yl.

To carry out the process according to the invention, on the one handpreferably those compounds of formula (IIa) are used, in which A isstraight-chained or branched C₂-C₂₀-alkylene, C₂-C₂₀-alkenylene,C₂-C₂₀-alkynylene, C₃-C₁₂-cycloalkylene, arylene or heterocyclylene;whereby the groups C₂-C₂₀-alkylene, C₂-C₂₀-alkenylene,C₂-C₂₀-alkynylene, C₃-C₁₂-cycloalkylene, arylene and heterocyclylene areoptionally substituted once or several times, independently of eachother, and the groups C₂-C₂₀-alkylene, C₂-C₂₀-alkenylene andC₂-C₂₀-alkynylene are optionally interrupted once or several times,independently of each other, by O, N—H or N—C₁-C₁₂-alkyl,C₃-C₉-cycloalkylene, arylene or heterocyclylene; or a group —D₁—D₂—D₃—;wherein

D₁ and D₃, independently of each other, signify optionally substitutedC₃-C₁₂-cycloalkylene or arylene and D₂ signifies C₂-C₂₀-alkylene,C₂-C₂₀-alkenylene, C₂-C₂₀-alkynylene, O, N—H or N—C₁-C₁₂-alkyl.

Particularly preferred bridging members A are C₂-C₁₂-alkylene,C₂-C₁₂-alkylene interrupted by one or two phenylene, cyclohexylene orpiperazinylene radicals; cyclohexylene or phenylene; or the group—D₁—D₂—D₃—, wherein D₁ and D₃ are phenylene or dicyclohexylene and D₂ isO or C₂-C₄-alkylene; A especially signifies C₂-C₄-alkylene.

On the other hand, in order to carry out the process according to theinvention, preferably compounds of formula (IIb) are used as thestarting material, wherein U is aryl, heterocyclyl, C₃-C₁₂-cycloalkyl ora group

wherein

A₁, A₂ and A₃ independently of one another, have the same significancesas given above for A in formula (IIa), and

X signifies N or CH.

Heterocyclyl A and U in the compounds of formulae (IIa) and (IIb) ispreferably an aromatic or non-aromatic, three- to ten-membered ring. Ifthe rings A and U are aromatic, they are preferably the same rings asdefined above for Het. If the rings A and U are non-aromaticheterocyclic rings, they are especially piperidinyl, piperazinyl,morpholinyl, pyrrolidinyl, tetrahydrofuranyl and dioxolanyl. Theradicals A₁, A₂ and A₃ independently of one another are most preferablyC₂-C₄-alkylene, especially ethylene.

A further object of the invention is

b) a method of producing a compound of formula (IIa) and (IIb), in whicha compound of formula

T—A—T  (IIIa),

 or of formula

wherein A and U have the same significance as defined above for formulae(IIa) and (IIb);

and R₂ has the same significance as defined above for formula (I);

and optionally the E/Z isomers, E/Z isomeric mixtures and/or tautomersthereof, each in free form or in salt form, is reacted when producing acompound of formula (IIIa) with two equivalents or when producing acompound of formula (IIIb) with three equivalents of a compound offormula

which is known or may be produced analogously to methods known per se,wherein R₁ and Het are defined as given above for formula (I) and Y is aleaving group, preferably in the presence of a base.

The following may be considered as the leaving group Y in the context ofthe described method of operation: halogen, preferably chlorine, bromineor iodine, especially chlorine, or sulfonic acid radicals, such asalkylsulfonic acid radicals, mesylate or tosylate.

The process step according to b) may be carried out preferably at normalor at a slightly raised pressure and in the presence of preferablyaprotic solvents or diluents. Suitable solvents or diluents are e.g.ethers and ether-type compounds, such as diethyl ether, dipropyl ether,dibutyl ether, dioxane, dimethoxyethane and tetrahydrofuran; aliphatic,aromatic and halogenated hydrocarbons, especially benzene, toluene,xylene, chloroform, methylene chloride, carbon tetrachloride andchlorobenzene; nitriles such as acetonitrile or propionitrile; dimethylsulfoxide or dimethyl formamide, as well as mixtures of these solvents.This process step is generally carried out at a temperature of −20° C.to +140° C., preferably between 0° C. and +120° C., preferably in thepresence of a base. Suitable bases are e.g. carbonates, such as sodiumand potassium carbonate. Hydrides may also be used as bases, for examplesodium hydride, potassium hydride and calcium hydride. If required, thereaction can also be carried out in the presence of a catalyst, e.g.cesium chloride.

A further object of the invention is

c) a method of producing the compounds of formula (IIa) and (IIIb), inwhich a compound of formula

H₂N—A—NH₂  (Va),

 or

and optionally the E/Z isomers, E/Z isomeric mixtures and/or tautomersthereof, each in free form or in salt form, wherein A and U have thesame significance as defined above for the compounds of formulae (IIa)and (IIb), and which are known or may be produced analogously to methodsknown per se, is reacted when producing a compound of formula (IIIa)either with two equivalents, or when producing a compound of formula(IIIb) with three equivalents of a compound of formula

which is known or may be produced analogously to methods known per se,and wherein R₂ has the same significance as defined for formula (I), inthe presence of an excess of formaldehyde or paraformaldehyde.

The process according to c) for the preparation of the compounds offormula (III) is advantageously carried out at normal pressure, but alsooptionally at a raised pressure in the presence of an inert solvent andat temperatures of between 0C and +140° C., preferably between +20° C.and +120° C. Suitable solvents are, in particular, alcohols such asmethanol, ethanol, and propanol, as well as water. Further suitablesolvents are e.g. aromatic hydrocarbons, such as benzene, toluene andxylene; ethers such as tetrahydrofuran, dioxane and diethyl ether,halogenated hydrocarbons such as methylene chloride, chloroform, carbontetrachloride and chlorobenzene, as well as other solvents which to notimpair the reaction. The solvents may also be used as mixtures. Theprocess is optionally effected adding an acidic catalyst, such as HCl,H₂SO₄ or a sulfonic acid, such as p-toluene-sulfonic acid. The resultingreaction water may be removed, if desired, using a water separator or byadding a molecular sieve.

A further object of the invention is

d) a method of producing a compound of formula (I), in which a compoundof formula (Va) or (Vb) is converted into a compound of formula (IIIa)or (IIIb) by reacting it with a compound of formula (VI) andformaldehyde or paraformaldehyde; this compound of formula (IIIa) or(IIIb) is converted by a compound of formula (IV) into a compound offormula (IIa) or (IIb) and this compound of formula (IIa) or (IIb) ishydrolysed.

Further objects of the invention are the compounds of formulae (IIa),(IIb), (IIIa) and (IIIb), and optionally the E/Z isomers, E/Z isomericmixtures and/or tautomers thereof, each in free form or in salt form, aswell as the use thereof in the preparation of compounds of formula (I).

Especially preferred embodiments of the method according to variants b)to d) may be taken from the examples.

The compounds of formula (I) produced according to the invention areknown. They are valuable active ingredients in pest control, that arewell tolerated by warm-blooded animals, fish and plants. The compoundsof formula (I) are especially suitable for the control of insects andarachnids, which appear on crops and ornamentals in agriculture,especially in cotton, vegetable and fruit plantations, in forestry, inthe protection of stock and material, as well as in the hygiene sector,especially on domestic animals and productive livestock. The compoundsare especially effective against plant-damaging sucking insects,especially against aphids and plant and leaf hoppers.

EXAMPLE P1.1

Preparation of the compound of formula

A mixture of 3.0 g of 1-methyl-2-nitroguanidine, 0.85 g of1,2-diaminoethane, 15 ml of dioxane and 5.7 ml of a 37% solution offormaldehyde in water at room temperature is heated to 50° C. andstirred at this temperature for 4 hours. The mixture is then evaporatedto dryness under vacuum, the residue stirred with diethyl ether and thetitle compound isolated by filtration. M.p. 222-223° C. (compound 1.1).

EXAMPLE P1.2

Preparation of the compound of formula

A mixture of 1.8 g of 1-methyl-2-nitroguanidine, 1.35 9 ofparaformaldehyde and 0.78 g of 1,5-diamino-3-oxa-pentane in 20 ml oftoluene and 20 ml of dioxane is mixed at room temperature with two dropsof a 37% solution of HCl in water, then heated to reflux temperature andstirred at this temperature for 6 hours. The mixture is then evaporatedto dryness under vacuum, the residue stirred with diethyl ether and thetitle compound isolated by filtration (compound 1.15).

EXAMPLE P1.3

Preparation of the compound of formula

A mixture of 8.0 g of 1-methyl-2-nitroguanidine and 3.0 g of1,4-diaminobutane in 25 ml of ethanol is mixed at room temperature with25 ml of a 37% solution of formaldehyde in water, heated to 50° C. andstirred at this temperature for 16 hours. Then, the mixture isevaporated to dryness under vacuum, and the residue is stirred withethanol. The title compound is obtained with a melting point of 232-234°C. (compound 1.4).

EXAMPLE P1.4

A mixture of 6.0 g of 1-methyl-2-nitroguanidine and 5.4 g of4,9dioxa-1,12-diaminododecane in 25 ml of ethanol is mixed at roomtemperature with 19 ml of a 37% solution of formaldehyde in water,heated to 50° C. and stirred at this temperature for 16 hours. Then, themixture is cooled to 5° C., filtered and the residue washed with alittle ethanol. The title compound is obtained with a melting point of140-143° C. (compound 1.14).

EXAMPLE P1.5

The following compounds listed in Table 1 can also be obtainedanalogously to the above methods of examples P1.1 to P1.4.

TABLE 1 Compounds of formula

No. A phys. data 1.1 —(CH₂)₂— m.p. 222-223° C. 1.2 —CH(CH₃)—CH₂— 1.3—(CH₂)₃— 1.4 —(CH₂)₄— m.p. 232-234° C. 1.5 —(CH₂)₅— 1.6 —(CH₂)₆— 1.7—(CH₂)₇— 1.8 —(CH₂)₈— 1.9 —(CH₂)₉— 1.10 —(CH₂)₁₀— 1.11 —(CH₂)₁₂— 1.12—CH₂—C(CH₃)₂—CH₂— 1.13 —CH₂—CH(OH)—CH₂— 1.14 —(CH₂)₃—O—(CH₂)₄—O—(CH₂)₃—m.p. 140-143° C. 1.15 —CH₂—CH₂—O—CH₂—CH₂— 1.16 —CH₂—CH(CH₃)—(CH₂)₃— 1.17—(CH₂)₂—O—(CH₂)₂—O—(CH₂)₂— 1.18 —(CH₂)₃—O—(CH₂)₂—O—(CH₂)₂—O—(CH₂)₃— 1.19—(CH₂)₃—N(CH₃)—(CH₂)₃— 1.20

1.21

1.22

1.23

1.24

1.25

1.26

1.27

1.28

1.29

1.30

EXAMPLE P2.1

Preparation of the compound of formula

A mixture of 2.4 g of 1-methyl-2-nitroguanidine and 1.0 g oftris(2-aminoethyl)amine in 50 ml of ethanol is mixed at room temperaturewith 30 ml of a 37% solution of formaldehyde in water, heated to 50° C.and stirred at this temperature for 16 hours. The mixture is thenevaporated to dryness under vacuum, the residue stirred with diethylether/ethyl acetate (1:1) and the title compound isolated by filtration(compound 2.1).

EXAMPLE P2.2

The following compounds listed in Table 2 can also be obtainedanalogously to the above method of example P2.1.

TABLE 2 Compounds of formula

No. A₁ A₂ A₃ X phys. data 2.1. —(CH₂)₂— —(CH₂)₂— —(CH₂)₂— N 2.2. —(CH₂)₃—CH₂— —(CH₂)₄ CH

EXAMPLE P3.1

Preparation of the compound of formula

A mixture of 2.0 g of the product obtainable according to example P1.1,1.6 g of 2-chloro-5-chloromethylpyridine and 2.8 g of potassiumcarbonate in 20 ml of dimethylformamide is stirred for 9 hours at 90° C.Then, the reaction mixture is filtered, the filtrate concentrated byevaporation under vacuum, and the residue taken up in 100 ml ofdichloromethane. The organic phase is washed with 50 ml of water and 50ml of saturated sodium chloride solution, dried over MgSO₄ andevaporated to dryness. The residue is stirred with diethyl ether and thetitle compound isolated by filtration (compound 10.B.1).

EXAMPLE P3.2

Preparation of the compound of formula

A mixture of 3.7 g of the compound obtainable according to example P1.3,3.2 g of 2-chloro-5-chloromethylpyridine and 5.5 g of potassiumcarbonate in 20 ml of dimethylformamide is stirred for 16 hours at 55°C. Then, the reaction mixture is filtered, the filtrate is concentratedby evaporation under vacuum, the residue is stirred in methanol andfiltration carried out. This yields the title compound with a meltingpoint of 178-180° C. (compound 10.B.4).

EXAMPLE P3.3

A mixture of 4.9 g of the compound obtainable according to example P1.4,3.24 g of 2-chloro-5-chloromethylpyridine and 5.5 g of potassiumcarbonate in 20 ml of dimethylformamide is stirred for 16 hours at 55°C. Then, the reaction mixture is filtered, the filtrate concentrated byevaporation under vacuum, and the residue purified on silica gel withethyl acetate/methanol (2:1) as eluant. This yields the title compoundwith a melting point of 70-72° C. (compound 10.B.14).

EXAMPLE P3.4

Compound of formula

A mixture of 2.0 9 of the compound obtainable according to example P1.1,1.95 g of 2-chloro-5-chloromethylthiazole, 4.0 g of potassium carbonateand 1.53 g of 18-Crown-6 (1,5,7,10,13,16-hexaoxacyclooctadecane) in 20ml of tetrahydrofuran is stirred for 24 hours at 50° C. Then, thereaction mixture is filtered, the filtrate concentrated by evaporationunder vacuum, and the residue purified on silica gel withdichloromethane/methanol (9:1) as eluant. This yields the title compoundwith a melting point of 175-178° C. (compound 3.B.1).

EXAMPLE P3.5

The following compounds listed in Tables 3 to 26 can also be obtainedanalogously to the above methods of examples P3.1 to P3.4.

TABLE B Compounds of formula

No. A B.1 —(CH₂)₂— B.2 —CH(CH₃)—CH₂— B.3 —(CH₂)₃— B.4 —(CH₂)₄— B.5—(CH₂)₅— B.6 —(CH₂)₆— B.7 —(CH₂)₇— B.8 —(CH₂)₈— B.9 —(CH₂)₉— B.10—(CH₂)₁₀— B.11 —(CH₂)₁₂— B.12 —CH₂—C(CH₃)₂—CH₂— B.13 —CH₂—CH(OH)—CH₂—B.14 —(CH₂)₃—O—(CH₂)₄—O—(CH₂)₃— B.15 —CH₂—CH₂—O—CH₂—CH₂— B.16—CH₂—CH(CH₃)—(CH₂)₃— B.17 —(CH₂)₂—O—(CH₂)₂—O—(CH₂)₂— B.18—(CH₂)₃—O—(CH₂)₂—O—(CH₂)₂—O—(CH₂)₃— B.19 —(CH₂)₃—N(CH₃)—(CH₂)₃— B.20

B.21

B.22

B.23

B.24

B.25

B.26

B.27

B.28

B.29

B.30

Table 3: Compounds of the general formula (IIc), wherein Het signifies

and A corresponds in each case to one line of Table B.

Compound 3.B.01: m.p. 175-178° C.

Table 4: Compounds of the general formula (IIc), wherein Het signifies

and A corresponds in each case to one line of Table B.

Table 5: Compounds of the general formula (IIc), wherein Het signifies

and A corresponds in each case to one line of Table B.

Table 6: Compounds of the general formula (IIc), wherein Het signifies

and A corresponds in each case to one line of Table B.

Table 7: Compounds of the general formula (IIc), wherein Het signifies2-methyl-tetrafuran-4-yl and A corresponds in each case to one line ofTable B.

Table 8: Compounds of the general formula (IIc), wherein Het signifiestetrafuran-3-yl and A corresponds in each case to one line of Table B.

Table 9: Compounds of the general formula (IIc), wherein Het signifies

and A corresponds in each case to one line of Table B.

Table 10: Compounds of the general formula (IIc), wherein Het signifies

and A corresponds in each case to one line of Table B.

Compound 10.B.04: m.p. 178-180° C.

Compound 10.B.14: m.p. 70-72° C.

Table 11: Compounds of the general formula (IIc), wherein Het signifiespyrid-3-yl and A corresponds in each case to one line of Table B.

Table 12: Compounds of the general formula (IIc), wherein Het signifies

and A corresponds in each case to one line of Table B.

Table 13: Compounds of the general formula (IIc), wherein Het signifies

and A corresponds in each case to one line of Table B.

Table 14: Compounds of the general formula (IIc), wherein Het signifies2,3-dichloropyrid-5-yl and A corresponds in each case to one line ofTable B.

TABLE C Compounds of formula

No. A₁ A₂ A₃ X C.1 —(CH₂)₂— —(CH₂)₂— —(CH₂)₂— N C.2 —(CH₂)₃ —CH₂——(CH₂)₄ CH

Table 15: Compounds of the general formula (IId), wherein Het signifies

and A₁, A₂, A₃ and X correspond in each case to one line of Table C.

Table 16: Compounds of the general formula (IId), wherein Het signifies

and A₁, A₂, A₃ and X correspond in each case to one line of Table C.

Table 17: Compounds of the general formula (IId), wherein Het signifies

and A₁, A₂, A₃ and X correspond in each case to one line of Table C.

Table 18: Compounds of the general formula (IId), wherein Het signifies

and A₁, A₂, A₃ and X correspond in each case to one line of Table C.

Table 19: Compounds of the general formula (IId), wherein Het signifies2-methyl-tetrahydrofuran-4-yl and A₁, A₂, A₃ and X correspond in eachcase to one line of Table C.

Table 20: Compounds of the general formula (IId), wherein Het signifies³-tetrahydrofuranyl and A₁, A₂, A₃ and X correspond in each case to oneline of Table C.

Table 21: Compounds of the general formula (IId), wherein Het signifies

and A₁, A₂, A₃ and X correspond in each case to one line of Table C.

Table 22: Compounds of the general formula (IId), wherein Het signifies2-chloro-pyrid-5-yl and A₁, A₂, A₃ and X correspond in each case to oneline of Table C.

Table 23: Compounds of the general formula (IId), wherein Het signifies3-pyridyl and A₁, A₂, A₃ and X correspond in each case to one line ofTable C.

Table 24: Compounds of the general formula (IId), wherein Het signifies

and A₁, A₂, A₃ and X correspond in each case to one line of Table C.

Table 25: Compounds of the general formula (IId), wherein Het signifies

A₁, A₂, A₃ and X correspond in each case to one line of Table C.

Table 26: Compounds of the general formula (IId), wherein Het signifies2,3-dichloropyrid-5-yl and A₁, A₂, A₃ and X correspond in each case toone line of Table C.

EXAMPLE 4.1

Preparation of the compound of formula

1.2 g of the compound obtainable according to example P3.1 are stirredfor 16 hours at room temperature together with 10 ml of methanol and 10ml of 1 n hydrochloric acid. The reaction mixture is concentrated todryness by evaporation and the residue purified on silica gel withdichloromethane/methanol (95:5) as the eluant. This yields the titleproduct with a melting point of 147-149° C. (compound 27.6).

EXAMPLE 4.2

Preparation of the compound of formula

1.2 g of the compound obtainable according to example P3.4 are stirredfor 40 hours at 50° C. together with 3.3 ml of methanol and 3.3 ml of 1n hydrochloric acid. The reaction mixture is evaporated to dryness andthe residue recrystallised from methanol. This yields the title productwith a melting point of 170-172° C. (compound 27.1).

EXAMPLE P4.3

The following compounds listed in Table 27 can also be obtainedanalogously to the above methods of examples 4.1 and 4.2.

TABLE 27 Compounds of the general formula

No. Het Phys. data 27.1

m.p. 170-172° C. 27.2

27.3 pyridyl 27.4

m.p. 166-168° C. 27.5

27.6 2-chloropyrid-5-yl 147-149° C. 27.7

27.8 2,3-dichloropyrid-5-yl m.p. 173-174° C. 27.9

27.10

27.11

27.12

A further object of the invention is a method of controlling pests,especially animal pests, particularly insects and members of the orderAcarina, using the compounds of formulae (IIa) and (IIb). The saidanimal pests include, for example, those which are mentioned in theEuropean Patent application EP-A-736'252. The pests mentioned thereinare thus included by reference in the object of the present invention.The method of controlling the said pests and the composition andpreparation of the corresponding pesticides are described inEP-A-736'252 and are included by reference in the object of the presentinvention.

What is claimed is:
 1. A compound of formula Q—A—Q  (IIa), wherein A isa direct bond, C₂-C₁₂-alkylene, C₂-C₁₂-alkylene interrupted by one ortwo phenylene, cyclohexylene or piperazinylene radicals; cyclohexyleneor phenylene; or the group —D₁—D₂—D₃—, wherein D₁ and D₃ are phenyleneor dicyclohexylene and D₂ is 0 or C₂-C₄-alkylene;

 wherein R₁ is hydrogen or C₁-C₄-alkyl; R₂ is hydrogen, C₁-C₆-alkyl,C₃-C₆-cycloalkyl; and Het is 2-chloropyrid-5-yl, tetrahydrofuran-3-yl,5-methyl-tetrahydrofuran-3-yl or 2-chloro-thiazol-5-yl; and optionallythe E/Z isomer, E/Z isomeric mixtures and/or tautomers thereof, each infree base form or in salt form.
 2. A method of controlling insects andmembers of the order Acarina, wherein a pesticidally effective amount ofthe compound of formula (IIa) as defined in claim 1, is applied to thepests or the locus thereof.